tbuckley/cabot-search huggingface dataset:
Abstract 14985: Artificial Intelligence Based Heart Rate Variability Analysis for Sudden Cardiac Arrest Risk Prediction
Authors: Noam Keidar, Yael Yaniv, Alex Bronstein, Gal Eidelsztein
Journal: Circulation (2022)

Introduction: Sudden Cardiac Arrest (SCA) is an unexpected life-threatening loss of cardiac function potentially leading to sudden cardiac death (SCD). It accounts for a half of cardiac mortality, posing a major public health problem. While SCA can be treated with implantable cardioverter defibrillators (ICD), most (80%) SCDs occur in relatively low risk patients, for whom risk benefit ratio of an ICD is unfavorable. Therefore, novel methods to identify high risk individuals and the time on which their risk is high may facilitate prevention of SCD. Methods : Long (~24h) ECG recordings from individuals who had an SCA on record (n=20), patients with other arrhythmias (n=84) and from healthy individuals (n=17) from PhysioNet databases were analyzed to extract inter beat intervals (IBI). For each step in the IBI series, 120 last IBIs were used to calculate 19 indices that quantify short term heart rate variability (HRV). An artificial intelligence model named temporal convolutional network (TCN) was used to continuously assess the risk of a future VF event based on the current HRV estimate combined with few hours of history of previous HRV estimates. Training and testing of the TCN was done using Leave One Out testing done twice. Patients being classified at any point in the record as high risk were considered high risk. Results : Only patients from the SCA population, and none from the other arrythmia and healthy patients, were classified as high risk (PPV=100%). On average, sensitivity and specificity were 62.5% and 100% respectively Conclusions : In this preliminary retrospective analysis, artificial intelligence based HRV analysis identified risk for a SCA event in the following 24 hours with high specificity. Larger cohort and prospective testing are needed to assess the clinical utility of such systems.
Abstract 15034: Prediction of Imminent Out-of-Hospital Sudden Cardiac Arrest Based on Warning Symptoms
Authors: Kyndaron Reinier, Bernadine Dizon, Harpriya Chugh, Ziana Bhanji, Madison Seifer, Tristan Grogan, David Elashoff, Chad Sorenson, Arayik S Sargsyan, Audrey Uy-Evanado, Faye L Norby, Angelo Salvucci, Jonathan Jui, Sumeet S Chugh
Journal: Circulation (2022)

Introduction: At least 50% of individuals with sudden cardiac arrest (SCA) have warning symptoms. However, such symptoms are also commonly experienced in the community. Comparisons with a control group, currently unavailable, are needed to establish utility of these symptoms for prediction of imminent SCA. Hypothesis: Symptoms documented by emergency medical services (EMS) prior to SCA vs. other 911 calls are distinct. Methods: We performed a case-control analysis from the ongoing Ventura, CA PRESTO study. Cases (ages 18-85) had witnessed SCA attended by EMS (2015-2021). SCA was defined as a sudden, unexpected pulseless condition of likely cardiac origin. Controls were identified from 911 calls that required transport by Ventura County EMS for emergency care but were not SCA. All cases and controls were required to have at least one symptom recorded by EMS that has been previously associated with acute coronary syndrome or SCA (Figure). Results: Among 553 witnessed cases with detailed EMS narratives, 411 (74%) had at least one inclusion symptom (mean age 66 y, 31% female). From a random subset of eligible EMS calls (n=2,794), 1171 controls had ≥1 symptom (mean age 61 y, 55% female). Among cases, dyspnea (41%) and chest pain (33%) were most common; prevalence of other symptoms was &lt;15%. Compared to controls, odds of chest pain, dyspnea, diaphoresis, and seizure-like activity were ≥45% higher in cases (p&lt;0.01) (Figure). Controls’ symptoms were less specific (nausea/vomiting, weakness, dizziness, abdominal symptoms), and palpitations (p&lt;0.01) (Figure). The sensitivity of chest pain (0.33) and dyspnea (0.41) for prediction of SCA was low, but specificities were higher (0.75 and 0.78, respectively). Conclusions: The prevalence of warning symptoms differed significantly between SCA cases and controls. However, sensitivity of individual symptoms was low; additional factors should be investigated to combine with warning symptoms to improve prediction of imminent SCA.
Multi-modality cardiac image computing: A survey
Authors: Lei Li, Wangbin Ding, Liqin Huang, Xiahai Zhuang, Vicente Grau
Journal: Medical Image Analysis (2023)

Multi-modality cardiac imaging plays a key role in the management of patients with cardiovascular diseases. It allows a combination of complementary anatomical, morphological and functional information, increases diagnosis accuracy, and improves the efficacy of cardiovascular interventions and clinical outcomes. Fully-automated processing and quantitative analysis of multi-modality cardiac images could have a direct impact on clinical research and evidence-based patient management. However, these require overcoming significant challenges including inter-modality misalignment and finding optimal methods to integrate information from different modalities. This paper aims to provide a comprehensive review of multi-modality imaging in cardiology, the computing methods, the validation strategies, the related clinical workflows and future perspectives. For the computing methodologies, we have a favored focus on the three tasks, i.e., registration, fusion and segmentation, which generally involve multi-modality imaging data, either combining information from different modalities or transferring information across modalities. The review highlights that multi-modality cardiac imaging data has the potential of wide applicability in the clinic, such as trans-aortic valve implantation guidance, myocardial viability assessment, and catheter ablation therapy and its patient selection. Nevertheless, many challenges remain unsolved, such as missing modality, combination of imaging and non-imaging data, and uniform analysis and representation of different modalities. There is also work to do in defining how the well-developed techniques fit in clinical workflows and how much additional and relevant information they introduce. These problems are likely to continue to be an active field of research and the questions to be answered in the future.
Prognostic impact of RUNX1 mutations and deletions in pediatric acute myeloid leukemia: results from the French ELAM02 study group
Authors: Lucille Lew-Derivry, Alice Marceau-Renaut, Laurène Fenwarth, Wendy Cuccuini, Paola Ballerini, Maxime Ferreboeuf, Audrey Guilmatre, Arnaud Petit, Virginie Gandemer, Fanny Rialland, Pascale Schneider, Gérard Michel, Yves Bertrand, Andre Baruchel, Claude Preudhomme, Guy Leverger, Hélène Lapillonne
Journal: Leukemia (2023)

Acute myeloid leukemia (AML) accounts for about 20% of acute leukemias in children and still has a poor prognosis compared to lymphoblastic leukemia (5-year survival rate about 68%) [1].Over the years, knowledge of oncogenetic abnormalities has improved, allowing AML to be classified into groups with different prognosis, leading to different treatment intensity [2].However, most genetic alterations have been described in adult cohorts.Bolouri et al. [3] and have shown that the molecular landscape in children differs from that of adult AMLs and further studies are needed for a comprehensive classification of pediatric AML.RUNX1, runt related transcription factor 1, is a transcription factor expressed in hematopoietic cells, plays a role in the early differentiation of progenitor and stem cells, and is known to be involved in hematologic diseases and leukemogenesis as a site of mutations [5].In adult AML cohorts, RUNX1 mutations are identified in 5-8% of younger patients, associated with M0 FAB subtype, normal karyotype and correlate with poor clinical outcome [6][7][8].As an unfavorable marker, adult patients with RUNX1 mutation are stratified in high risk group of treatment [9].In contrast to RUNX1 mutations, RUNX1 deletions have rarely been studied and their impact is therefore unknown.In children, the impact of RUNX1 mutations or deletions remains unclear because of their low frequency and is not used for risk stratification and choice of treatment intensity.438 children with de novo AML were treated in the ELAM02 trial and RUNX1 gene status was screened in 386 of them.RUNX1 abnormality was found in 8% (29 of 386) of the cases, 24 patients with mutation and 5 with deletion.Because the majority of RUNX1 mutations in AML behave as loss-of-function mutations,
Yield of Serial Testing for Tuberculosis Exposure in Patients With Inflammatory Bowel Diseases: One Test is Not Enough
Authors: Sean L. Lapp, Meenakshi Bewtra, James D. Lewis, Manreet Kaur, Themistocles Dassopoulos, Scott B. Snapper, Joshua R. Korzenik, Matthew Bohm, Laura Raffals, Beniwal-Patel Poonam, David Hudesman, Kirk Russ, Loren Brook, Joel Pekow, Raymond Cross, Uni Wong, Shrinivas Bishu, Meenakshi Bewtra, James D. Lewis, Richard Duerr, Sumona Saha, Freddy Caldera, Elizabeth Scoville, Parakkal Deepak, Matthew Ciorba
Journal: Clinical Gastroenterology and Hepatology (2023)
Virion glycosylation influences mycobacteriophage immune recognition
Authors: Krista G. Freeman, Anna C. Robotham, Olivia B. Parks, Lawrence Abad, Deborah Jacobs-Sera, Michael J. Lauer, Jennifer M. Podgorski, Yu Zhang, John V. Williams, Simon J. White, John F. Kelly, Graham F. Hatfull, Welkin H. Pope
Journal: Cell Host & Microbe (2023)

Glycosylation of eukaryotic virus particles is common and influences their uptake, trafficking, and immune recognition. In contrast, glycosylation of bacteriophage particles has not been reported; phage virions typically do not enter the cytoplasm upon infection, and they do not generally inhabit eukaryotic systems. We show here that several genomically distinct phages of Mycobacteria are modified with glycans attached to the C terminus of capsid and tail tube protein subunits. These O-linked glycans influence antibody production and recognition, shielding viral particles from antibody binding and reducing production of neutralizing antibodies. Glycosylation is mediated by phage-encoded glycosyltransferases, and genomic analysis suggests that they are relatively common among mycobacteriophages. Putative glycosyltransferases are also encoded by some Gordonia and Streptomyces phages, but there is little evidence of glycosylation among the broader phage population. The immune response to glycosylated phage virions in mice suggests that glycosylation may be an advantageous property for phage therapy of Mycobacterium infections.
CD36 Drives Metastasis and Relapse in Acute Myeloid Leukemia
Authors: Thomas Farge, Jean Nakhle, Damien Lagarde, Guillaume Cognet, Nathaniel Polley, Rémy Castellano, Marie-Laure Nicolau, Claudie Bosc, Marie Sabatier, Ambrine Sahal, Estelle Saland, Yannick Jeanson, Nathan Guiraud, Emeline Boet, Camille Bergoglio, Mathilde Gotanègre, Pierre-Luc Mouchel, Lucille Stuani, Clément Larrue, Marie Sallese, Véronique De Mas, Cedric Moro, Cédric Dray, Yves Collette, Isabelle Raymond-Letron, Isabelle Ader, Christian Récher, Jean-Emmanuel Sarry, Florence Cabon, François Vergez, Audrey Carrière
Journal: Cancer Research (2023)

Identifying mechanisms underlying relapse is a major clinical issue for effective cancer treatment. The emerging understanding of the importance of metastasis in hematologic malignancies suggests that it could also play a role in drug resistance and relapse in acute myeloid leukemia (AML). In a cohort of 1,273 AML patients, we uncovered that the multifunctional scavenger receptor CD36 was positively associated with extramedullary dissemination of leukemic blasts, increased risk of relapse after intensive chemotherapy, and reduced event-free and overall survival. CD36 was dispensable for lipid uptake but fostered blast migration through its binding with thrombospondin-1. CD36-expressing blasts, which were largely enriched after chemotherapy, exhibited a senescent-like phenotype while maintaining their migratory ability. In xenograft mouse models, CD36 inhibition reduced metastasis of blasts and prolonged survival of chemotherapy-treated mice. These results pave the way for the development of CD36 as an independent marker of poor prognosis in AML patients and a promising actionable target to improve the outcome of patients.CD36 promotes blast migration and extramedullary disease in acute myeloid leukemia and represents a critical target that can be exploited for clinical prognosis and patient treatment.
Sublethal necroptosis signaling promotes inflammation and liver cancer
Authors: Mihael Vucur, Ahmed Ghallab, Anne T. Schneider, Arlind Adili, Mingbo Cheng, Mirco Castoldi, Michael T. Singer, Veronika Büttner, Leonie S. Keysberg, Lena Küsgens, Marlene Kohlhepp, Boris Görg, Suchira Gallage, Jose Efren Barragan Avila, Kristian Unger, Claus Kordes, Anne-Laure Leblond, Wiebke Albrecht, Sven H. Loosen, Carolin Lohr, Markus S. Jördens, Anne Babler, Sikander Hayat, David Schumacher, Maria T. Koenen, Olivier Govaere, Mark V. Boekschoten, Simone Jörs, Carlos Villacorta-Martin, Vincenzo Mazzaferro, Josep M. Llovet, Ralf Weiskirchen, Jakob N. Kather, Patrick Starlinger, Michael Trauner, Mark Luedde, Lara R. Heij, Ulf P. Neumann, Verena Keitel, Johannes G. Bode, Rebekka K. Schneider, Frank Tacke, Bodo Levkau, Twan Lammers, Georg Fluegen, Theodore Alexandrov, Amy L. Collins, Glyn Nelson, Fiona Oakley, Derek A. Mann, Christoph Roderburg, Thomas Longerich, Achim Weber, Augusto Villanueva, Andre L. Samson, James M. Murphy, Rafael Kramann, Fabian Geisler, Ivan G. Costa, Jan G. Hengstler, Mathias Heikenwalder, Tom Luedde
Journal: Immunity (2023)

It is currently not well known how necroptosis and necroptosis responses manifest in vivo. Here, we uncovered a molecular switch facilitating reprogramming between two alternative modes of necroptosis signaling in hepatocytes, fundamentally affecting immune responses and hepatocarcinogenesis. Concomitant necrosome and NF-κB activation in hepatocytes, which physiologically express low concentrations of receptor-interacting kinase 3 (RIPK3), did not lead to immediate cell death but forced them into a prolonged "sublethal" state with leaky membranes, functioning as secretory cells that released specific chemokines including CCL20 and MCP-1. This triggered hepatic cell proliferation as well as activation of procarcinogenic monocyte-derived macrophage cell clusters, contributing to hepatocarcinogenesis. In contrast, necrosome activation in hepatocytes with inactive NF-κB-signaling caused an accelerated execution of necroptosis, limiting alarmin release, and thereby preventing inflammation and hepatocarcinogenesis. Consistently, intratumoral NF-κB-necroptosis signatures were associated with poor prognosis in human hepatocarcinogenesis. Therefore, pharmacological reprogramming between these distinct forms of necroptosis may represent a promising strategy against hepatocellular carcinoma.
Abstract 15047: Survival With Favorable Neurological Outcome and Quality of CPR Following In-Hospital Cardiac Arrest in Children With Cardiac Disease Compared to Non-Cardiac Disease
Authors: Myke Federman, Chella Palmer, Robert A Berg, Deborah Franzon, Kathryn Graham, Leanna L Huard, Theresa Kirkpatrick, Vinay M Nadkarni, Laura A Maitoza, Ryan W Morgan, Matthew Sharron, Heather Wolfe, Robert M Sutton, Maryam Y Naim
Journal: Circulation (2022)

Introduction: Children with cardiac disease have higher rates of in hospital cardiac arrest (IHCA) compared to non-cardiac disease. We aimed to determine differences in survival in children with medical and surgical cardiac compared to non-cardiac disease following IHCA and to assess whether CPR quality was different between groups. Hypothesis: We hypothesized: 1) medical cardiac have worse and surgical cardiac have improved outcomes compared to non-cardiac patients, and 2) CPR quality is similar between groups. Methods: A secondary analysis of the ICU-RESUS citation project ( ICU-RESUS ; NCT02837497) was conducted. The primary outcome was survival to hospital discharge with favorable neurological outcome defined as a Pediatric Cerebral Performance Category score of 1 - 3 or no change from baseline. Secondary outcomes included physiologic measures of intra-arrest quality. Results: Of 1100 children with IHCA, 273 (25%) were medical cardiac, 383 (35%) were surgical cardiac, and 444 (40%) were non-cardiac. The medical cardiac group was less likely to survive with favorable outcome compared to the non-cardiac group (48% vs. 55%, aOR 0.59, CI 95 0.40, 0.88). There was no difference in outcome between the surgical cardiac (58%) and non-cardiac group. There were no differences in chest compression (CC) rate, CC fraction, ventilation rate, intra-arrest average target diastolic blood pressure or average target systolic blood pressure between medical cardiac vs. non-cardiac and surgical cardiac vs. non-cardiac groups. The surgical cardiac group was less likely to achieve target CC depth compared to non-cardiac group (OR 0.15, CI 95 0.02, 0.52). There was no difference in CC depth in medical cardiac vs. non-cardiac groups. Conclusions: In this large study of pediatric IHCA, medical cardiac patients had lower survival with favorable neurologic outcome compared to non-cardiac patients. Surgical cardiac patients had similar outcome to non-cardiac patients. CPR quality was similar in medical-cardiac and non-cardiac patients, however delivered CC depths were lower in surgical cardiac compared to non-cardiac patients.
Correction: The phospholipid transporter PITPNC1 links KRAS to MYC to prevent autophagy in lung and pancreatic cancer
Authors: Rodrigo Entrialgo‑Cadierno, Cristina Cueto‑Ureña, Connor Welch, Iker Feliu, Irati Macaya, Laura Vera, Xabier Morales, Sandra Vietti Michelina, Pietro Scaparone, Ines Lopez, Elodie Darbo, Oihane Erice, Adrian Vallejo, Haritz Moreno, Ainhoa Goñi‑Salaverri, David Lara‑Astiaso, Nils Halberg, Ivan Cortes‑Dominguez, Elizabeth Guruceaga, Chiara Ambrogio, Fernando Lecanda, Silve Vicent
Journal: Molecular Cancer (2023)
Artificial intelligence in digital pathology of cutaneous lymphomas: A review of the current state and future perspectives
Authors: Thom Doeleman, Liesbeth M. Hondelink, Maarten H. Vermeer, Marijke R. van Dijk, Anne M.R. Schrader
Journal: Seminars in Cancer Biology (2023)

Primary cutaneous lymphomas (CLs) represent a heterogeneous group of T-cell lymphomas and B-cell lymphomas that present in the skin without evidence of extracutaneous involvement at time of diagnosis. CLs are largely distinct from their systemic counterparts in clinical presentation, histopathology, and biological behavior and, therefore, require different therapeutic management. Additional diagnostic burden is added by the fact that several benign inflammatory dermatoses mimic CL subtypes, requiring clinicopathological correlation for definitive diagnosis. Due to the heterogeneity and rarity of CL, adjunct diagnostic tools are welcomed, especially by pathologists without expertise in this field or with limited access to a centralized specialist panel. The transition into digital pathology workflows enables artificial intelligence (AI)-based analysis of patients' whole-slide pathology images (WSIs). AI can be used to automate manual processes in histopathology but, more importantly, can be applied to complex diagnostic tasks, especially suitable for rare disease like CL. To date, AI-based applications for CL have been minimally explored in literature. However, in other skin cancers and systemic lymphomas, disciplines that are recognized here as the building blocks for CLs, several studies demonstrated promising results using AI for disease diagnosis and subclassification, cancer detection, specimen triaging, and outcome prediction. Additionally, AI allows discovery of novel biomarkers or may help to quantify established biomarkers. This review summarizes and blends applications of AI in pathology of skin cancer and lymphoma and proposes how these findings can be applied to diagnostics of CL.
Author Correction: Systemic GDF11 attenuates depression-like phenotype in aged mice via stimulation of neuronal autophagy
Authors: Carine Moigneu, Soumia Abdellaoui, Mariana Ramos-Brossier, Bianca Pfaffenseller, Bianca Wollenhaupt-Aguiar, Taiane de Azevedo Cardoso, Claire Camus, Aurélie Chiche, Nicolas Kuperwasser, Ricardo Azevedo da Silva, Fernanda Pedrotti Moreira, Han Li, Franck Oury, Flávio Kapczinski, Pierre-Marie Lledo, Lida Katsimpardi
Journal: Nature Aging (2023)
Erratum to: Post-transcriptional control of haemostatic genes: mechanisms and emerging therapeutic concepts in thrombo-inflammatory disorders
Journal: Cardiovascular Research (2023)

A growing number of studies document a contribution of miRNAs to the regulation of haemostatic [136][137][138][139] and thrombotic 123,135,[138][139][140][141] functions. The sentence has now been corrected to read as follows:A growing number of studies document a contribution of miRNAs to the regulation of haemostatic [135][136][137][138][139] and thrombotic 123,135,[138][139][140][141] functions.In addition, upon original publication, the colour coding of gene names was inadvertently omitted from the HTML version of Table 2, and it has now been restored.
Activin A–Mediated Polarization of Cancer-Associated Fibroblasts and Macrophages Confers Resistance to Checkpoint Immunotherapy in Skin Cancer
Authors: Christine Pich-Bavastro, Laura Yerly, Jeremy Di Domizio, Stéphanie Tissot-Renaud, Michel Gilliet, François Kuonen
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Cemiplimab is approved for the treatment of locally advanced basal cell carcinomas (BCC), although with mitigated results. We sought to interrogate the cellular and molecular transcriptional reprogramming underlying BCC resistance to immunotherapy. Experimental Design: Here, we combined spatial and single-cell transcriptomics to deconvolute the spatial heterogeneity of the tumor microenvironment in regard with response to immunotherapy, in a cohort of both naïve and resistant BCCs. Results: We identified subsets of intermingled cancer-associated fibroblasts (CAF) and macrophages contributing the most to CD8 T-cell exclusion and immunosuppression. Within this spatially resolved peritumoral immunosuppressive niche, CAFs and adjacent macrophages were found to display Activin A–mediated transcriptional reprogramming towards extracellular matrix remodeling, suggesting active participation to CD8 T-cell exclusion. In independent datasets of human skin cancers, Activin A–conditioned CAFs and macrophages were associated with resistance to immune checkpoint inhibitors (ICI). Conclusions: Altogether, our data identify the cellular and molecular plasticity of tumor microenvironment (TME) and the pivotal role of Activin A in polarizing the TME towards immune suppression and ICI resistance.